Participants randomized to the 1350 mg/day group will begin with a dose of 450 mg, increasing bi-weekly to a dose of 1350 mg/day.

Participants receive capsules visually identical to the experimental groups but without active ingredients.

Lewy Body Disease

The treatment regimen consists of a titration phase and a maintenance phase. Participants begin the titration phase (Weeks 1 and 2) taking 6 capsules a day (450mg or 0 mg) divided BID (3 capsules in the morning and 3 capsules in the evening). The first medication dose will be taken at the end of Baseline visit and in the presence of the study Neurologist. Possible side effects will be observed for 30 minutes. Medication dose will increase bi-weekly to 12 capsules on Weeks 3 and 4, and 18 capsules on Weeks 5 and 6 divided BID. At the end of titration (Week 5) participants will have reached a maximum of 1350mg or 0mg per day, depending on group allocation. In the maintenance phase, participants will remain in their maximum dose (1350mg or 0mg) from Week 5 to Week 52 (End of Trial).

Ambroxol Hydrochloride

Placebo

Parkwood Institute

Ambroxol as a Novel Disease Modifying Treatment for Lewy Body Dementia

Monitor safety using frequent cognitive evaluations using the mini mental state examination. Lower scores are indicative of worsening cognitive impairment [score range: 0-30]

Change in the number of participants with AE's and SAE's

Change from baseline in the number of participants with treatment and/or study discontinuation will be used to demonstrate safety and tolerability

Change from baseline in the number of participants with clinically significant ECG abnormalities (QT interval) to demonstrate safety

Changes in hemodynamic values from baseline over time to demonstrate safety

Change from baseline in number of participants with abnormal changes in clinical laboratory blood tests from baseline over time for safety

Change from baseline in number of participants with abnormal changes in clinical laboratory urine tests from baseline over time for safety

Change in plasma Ambroxol concentrations from blood sample from baseline

Change in Ambroxol concentrations from cerebrospinal fluid sample from baseline

Change in GCase concentration in the CSF from baseline

Change in white blood cell GCase concentrations from baseline

Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits. Lower scores are indicative of worsening cognitive function [score range: 40-160]

Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits. Patients are assessed as: no change, minimal, moderate and marked worsening, minimal, moderate and marked improvement

Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits. Lower scores are indicative of worsening cognitive impairment [score range: 0-30]

Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits: Higher times to complete are indicative of worsening cognitive function [Max time: 300 seconds]

Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits. Lower scores are indicative of higher cognitive dysfunction [Score range: 0-134]

Change in levels of plasma biomarkers: α-synuclein (pg/ml), Tau (pg/ml), phospho-Tau (pg/ml) and beta amyloid-42 (pg/ml) in plasma

Change in levels of CSF biomarkers: α-synuclein (pg/ml), Tau (pg/ml), phospho-Tau (pg/ml) and beta amyloid-42 (pg/ml) in CSF

Demonstrate change or slowed progression in standard tests of mood and neuropsychiatric symptoms. Assesses frequency and severity of neuropsychological symptoms with higher scores indicative of more symptoms, higher frequency and more severe. [Score range: 0-144]

Demonstrate change or slowed progression in standard tests of mood and neuropsychiatric symptoms: Higher scores indicate more severe depression [score range: 0-15]

Demonstrate change or slowed progression in tests of motor function/Parkinsonism: Higher scores indicate more dysfunction [score range: 0-108]

Demonstrate change or slowed progression in tests of motor function/Parkinsonism. Higher times indicate slower movement and more motor impairment

Stephen Pasternak

Neurologist

Lawson Health Research Institute

Participants randomized to the 1050 mg/day group will begin with a dose of 225mg (3 mg/kg/day), increasing bi-weekly by ~3mg/kg to a dose of 1050 mg/day (~l5 mg/kg/day).

Parkinson's Disease Dementia

Ambroxol

Ambroxol as a Treatment for Parkinson's Disease Dementia

Ambroxol as a Novel Disease Modifying Treatment for Parkinson's Disease Dementia

This 70-point test examines language, recall, word finding, comprehension, naming, drawing, praxis, orientation, and word recognition. Although designed for Alzheimer's disease where it is considered a gold standard, the ADAS-Cog has been used effectively in many clinical trials of PDD including large randomized trials. This scale has been recommended for the assessment of Parkinson's dementia in "Diagnostic Procedures for Parkinson's Disease Dementia: Recommendations from the Movement Disorder Society Task Force"

This is a 7-point scale for rating patient function in cognition behavior and activities of daily living, and this test is standard in clinical trials in Alzheimer's disease and has been useful in trials with PDD.

gait assessment on electronic mat (Zeno Walkway System)

levels of α-synuclein (pg/ml), Tau (pg/ml), phospho-Tau (pg/ml) and beta amyloid-42 (pg/ml)

glucocerebroside/seizures

Ambroxol as a Novel Disease Modifying Treatment for Lewy Body Dementia

Ambroxol as a Treatment for Parkinson's Disease Dementia

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